Monoclonal Antibody FDA Approval for Pediatric Population



Amy Paller, MD: We're very excited that dupilumab has recently been approved by the Food and Drug Administration for children as young as 6 years. We know that the pathomechanism of atopic dermatitis across the board, at any age, is strongly involving the activation of Th2 [T helper cell type 2] immunity. Dupilumab, of course, targets the interleukin-4 [IL-4] receptor, which is the receptor that needs to be activated for us to have atopic dermatitis. It's activated by both IL-4 and IL-13. And we've seen great success in many patients who are adults or teenagers, and now certainly in school age children as well, with the use of the dupilumab as the first biologic that's been approved for atopic dermatitis.

The pivotal clinical trial that led to the approval of the 6-to-11-year-old age group for dupilumab was a randomized, double-blind, placebo-controlled phase 3 trial that included only children in that age group who had severe atopic dermatitis. Previous trials, of course, included moderate to severe. But here the bar was raised for even enrolling children in that trial. The children were allowed to use topical corticosteroids during the trial and were randomized, either to get placebo or to get the drug. And the drug was administered based on weight.

There were 2 arms of the 3 arms that included the drug itself. Those children who were less than 30 kg were randomized to either receive 300 mg every 4 weeks or 100 mg every 2 weeks. Those children who were 30 kg or above were randomized either to receive the 300 mg every 4 weeks, not weight based, or 200 mg every 2 weeks. And those children were followed for 16 weeks on this regimen for assessment and then went on as desired into the open-label phase.

As with all of the other trials with dupilumab, it performed very well. And obviously, that was important and led to the approval of the drug. What we find is that interestingly, all of the treatment groups with the dupilumab did quite well, but there were some differences based on the weight of the child that led to some differences in the indication that was chosen with the FDA for dosing for this drug based on weight. What we found overall was an investigator global assessment of clear or almost clear in about 30% of the children across the board.

We saw an EASI-75 [Eczema Area and Severity Index score improvement of 75%] in the chosen doses. The mean reduction in EASI score was 80%. We also saw tremendous changes, significant changes, in the quality of life based on the Children’s Dermatology Life Quality Index. We of course saw a reduction in itch. In fact, about 55% of the children achieved a reduction in peak itch NRS [Numerical Rating Scale] of at least 4. Sleep was improved. The Patient-Oriented Eczema Measure scores were improved.

Everything improved in this study. Now, it was interesting because when we looked at the different results based on weight, it wasn't the same. We found that in those children who were under 30 kg, the children taking 300 mg every 4 weeks performed better than the 100 mg every 2 weeks. It was the opposite in the children who were 30 kg or above. The children taking the drug every 2 weeks, 200 mg performed better than the 300 mg every 4 weeks. And that was interesting, as well, because it correlated with the trough concentrations at week 16, which were considerably higher in the younger kids with 300 mg every 4 weeks and considerably higher with the weightier kids at 200 mg every 2 weeks. So those were the dosages that were then chosen with the FDA for moving forward.

So now children who are 6-to-11-years-of-age with either moderate or severe atopic dermatitis, even though the trials were done with just severe, are able to get the dupilumab on label. And that's a great thing.

Transcript Edited for Clarity

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